Office Action Predictor
Application No. 18/037,472

SYSTEM AND METHOD FOR MEASURING BLOOD FLOW VELOCITY ON A MICROFLUIDIC CHIP

Non-Final OA §103
Filed
May 17, 2023
Examiner
BEZUAYEHU, SOLOMON G
Art Unit
2674
Tech Center
2600 — Communications
Assignee
Case Western Reserve University
OA Round
2 (Non-Final)
75%
Grant Probability
Favorable
2-3
OA Rounds
3y 4m
To Grant
99%
With Interview

Examiner Intelligence

75%
Career Allow Rate
461 granted / 614 resolved
Without
With
+34.8%
Interview Lift
avg trend
3y 4m
Avg Prosecution
34 pending
648
Total Applications
career history

Statute-Specific Performance

§101
16.0%
-24.0% vs TC avg
§103
49.6%
+9.6% vs TC avg
§102
13.5%
-26.5% vs TC avg
§112
11.7%
-28.3% vs TC avg
Black line = Tech Center average estimate • Based on career data

Office Action

§103
DETAILED ACTION Response to Arguments Applicant’s arguments with respect to 103 rejections have been fully considered and are persuasive. The rejection of claims has been withdrawn. Claim Rejections - 35 USC § 103 The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action: A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made. Claims 1 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over (Yeom “Microfluidic system for monitoring temporal variations of hemorheological properties and platelet adhesion in LPS-injected rats”) in view of Schmidt (“improvements in the accuracy of wavelet-based optical flow velocimetry (wOFV) using an efficient and physically based implementation of velocity regularization”). Regarding Claim 12, Yeom teaches a method of determining one or more hemodynamics of a blood sample, the method comprising: obtaining a plurality of images (flow images) of the blood sample (blood, blood samples) flowing through a microchannel (microfluidic channel, stenosed microchannel) of a microfluidic device [Page 2 Para 7 “a microfluidic channel with a stenosis is employed to accentuate platelet activation. Blood is stably supplied into the stenosed microchannel at a flow rate of 1mL/h”; Page 8 “Flow images in the microfluidic devices are consecutively captured with a high-speed camera (FASTCAM SA 1.1, Photron Ltd., San Diego, CA, USA) at a frame rate of 5000 fps.”]; and determining one or more hemodynamic parameters (hemorheological properties, microrheological parameters, flow rate) based on differences between two sets of consecutive images (pair) of the plurality of images, wherein a processor uses particle image velocimetry (PIV) (micro-piv technique, micro-particle image velocimetry (piv)) processing of a first set of consecutive images to determine temporal evolution of mean blood flow velocity (temporal variation in flow rate of blood samples) [Page 2, “Specifically, a correlation map labels the 2D correlation coefficient (R) in the small tiles of two consecutive images captured with a time interval Δt.”; Page 8 “a micro-PIV technique is employed to measure velocity field of the flow using the cross-correlation PIV algorithm to each image pair”; Page 5 “Temporal variation in flow rate of blood samples estimated by micro-PIV technique”; fig. 3 and related description]. However, Yeom teaches correlation based micro-PIV and correlation maps for hemorheological analysis and velocity field, but does not explicitly teach wavelet-based optical flow velocimetry (wOFV) processing of the second set of consecutive images to determine a blood flow velocity field. Schmidt teaches a wavelet-based optical flow velocimetry (wOFV) (wavelet-based optical flow velocimetry (wOFV) method) processing of the second set of consecutive images (synthetic tracer particle images, experimental particle image data) to determine a blood flow velocity field (velocity field) [Abstract “This manuscript details recent improvements in a wavelet-based optical flow velocimetry (wOFV) method that represents a more physically sound implementation and results in increased accuracy of the velocity estimation”; “Velocity fields are estimated from synthetic tracer particle images generated from 2D DNS of isotropic turbulence and from experimental results from a turbulent flow”]. It would have been obvious to one of ordinary skill in the art before the effective filing date to modify Yeom to teach wavelet-based optical flow velocimetry processing of the second set of consecutive images to determine a blood flow velocity field, feature as taught by Schmidt; because the modification enables to obtain higher-resolution, more accurate blood flow velocity fields and additional hemodynamic parameters from the same sets of microfluidic blood-flow images. Regarding Claims 17 and 7, Yeom teaches segmenting a first image and a second image of the first set of images into a plurality of interrogation regions, cross-correlating each of the plurality of interrogation regions, and identifying one more velocity vectors based on the cross-correlated interrogation regions for PIV [Page. 8 “a micro-PIV technique is employed to measure velocity field of the flow using the cross-correlation PIV algorithm to each image pair. The size of each interrogation window is 32×32 pixels with 50% overlapping. The obtained velocity fields are filtered using a 3×3 median kernel”]. Regarding Claims 19 and 9, Yeom teaches wherein the microchannel has at least one functionalized adhesion region adapted to adhere to blood cells of interest within the blood sample [Page 8 “To facilitate platelet adhesion, the glass substrate is coated with collagen and the flow acceleration is induced in the stenosed channel”]. Claims 2 and 13 are rejected under 35 U.S.C. 103 as being unpatentable over (Yeom “Microfluidic system for monitoring temporal variations of hemorheological properties and platelet adhesion in LPS-injected rats”) in view of Schmidt (“improvements in the accuracy of wavelet-based optical flow velocimetry (wOFV) using an efficient and physically based implementation of velocity regularization”) further in view of Schallek et al. (pub. No. US 20190114790). Regarding Claims 13 and 2, Yeom in view of Schmidt doesn’t explicitly teach the claim limitation. However, Schallek et al. (pub. No. US 20190114790) teaches estimating flow velocity for the PIV and wOFV by identifying individual blood cells of the flowing blood sample [Para. 57]. It would have been obvious to one of ordinary skill in the art before the effective filing date to modify Yeom in view of Schmidt to teach the claim limitation, feature as taught by Schallek; because the modification enables the user to monitor bodily fluid parameters using a mobile electronic device. Claims 3 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over (Yeom “Microfluidic system for monitoring temporal variations of hemorheological properties and platelet adhesion in LPS-injected rats”) in view of Schmidt (“improvements in the accuracy of wavelet-based optical flow velocimetry (wOFV) using an efficient and physically based implementation of velocity regularization”), further in view of Sadaba Champetier De Ribes et al. (Pub. No. US 2011/0039285). Regarding Claims 14 and 3, Yeom in view of Schmidt doesn’t explicitly teach the claim limitation. However, Sadaba teaches calculating clotting time and decay rate based on the temporal evolution of the mean flow velocity determined by PIV [Para. 30 and 31]. It would have been obvious to one of ordinary skill in the art before the effective filing date to modify Yeom in view of Schmidt to teach the claim limitation, feature as taught by Sadaba; because the modification enables making blood clothing tests cheap, simple, and Patient operable. Claims 4 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over (Yeom “Microfluidic system for monitoring temporal variations of hemorheological properties and platelet adhesion in LPS-injected rats”) in view of Schmidt (“improvements in the accuracy of wavelet-based optical flow velocimetry (wOFV) using an efficient and physically based implementation of velocity regularization”), further in view of Jain et al. (Pub. No. US 2018/0185839). Regarding Claims 15 and 4, Yeom in view of Schmidt doesn’t explicitly teach the claim limitation. However, Jain teaches identifying blood flow channels around thrombi formed in the microchannel by the velocity field generated by wOFV [Para. 99]. It would have been obvious to one of ordinary skill in the art before the effective filing date to modify Yeom in view of Schmidt to teach the claim limitation, feature as taught by Jain; because the modification enables to solve the lack of real time patient specific whole blood coagulation test that reflect actual vascular shear conditions, by using a microfluidic multi-channel device that monitors pressure. Claims 5 and 6 are rejected under 35 U.S.C. 103 as being unpatentable over (Yeom “Microfluidic system for monitoring temporal variations of hemorheological properties and platelet adhesion in LPS-injected rats”) in view of Schmidt (“improvements in the accuracy of wavelet-based optical flow velocimetry (wOFV) using an efficient and physically based implementation of velocity regularization”), further in view of Roth (Pub. No. US 2012/0002875). Regarding Claims 5, and 6, Yeom in view of Schmidt doesn’t explicitly teach the claim limitation. However, Roth teaches applying one of mean filtering, intensity normalization, and edge-aware Laplacian filtering to the images prior to PIV and/or wOFV [Para. 12]. It would have been obvious to one of ordinary skill in the art before the effective filing date to modify Yeom in view of Schmidt to teach the claim limitation, feature as taught by Roth; because the modification enables to solve the lack of real time patient specific whole blood coagulation test that reflect actual vascular shear conditions, by using a microfluidic multi-channel device that monitors pressure. Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over (Yeom “Microfluidic system for monitoring temporal variations of hemorheological properties and platelet adhesion in LPS-injected rats”) in view of Schmidt (“improvements in the accuracy of wavelet-based optical flow velocimetry (wOFV) using an efficient and physically based implementation of velocity regularization”) further in view of Schallek et al. (pub. No. US 20190114790) and further in view of Roth (Pub. No. US 2012/0002875). Regarding Claim 16, Yeom in view of Schmidt and Schallek doesn’t explicitly teach the claim limitation. However, Roth teaches applying one of mean filtering, intensity normalization, and edge-aware Laplacian filtering to the images prior to PIV and/or wOFV [Para. 12]. It would have been obvious to one of ordinary skill in the art before the effective filing date to modify Yeom in view of Schmidt and Schallek to teach the claim limitation, feature as taught by Roth; because the modification enables to solve the lack of real time patient specific whole blood coagulation test that reflect actual vascular shear conditions, by using a microfluidic multi-channel device that monitors pressure. Claims 18 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over (Yeom “Microfluidic system for monitoring temporal variations of hemorheological properties and platelet adhesion in LPS-injected rats”) in view of Schmidt (“improvements in the accuracy of wavelet-based optical flow velocimetry (wOFV) using an efficient and physically based implementation of velocity regularization”), further in view of Falahatpisheh et al. (Pub. No. (US 2018/0253854). Regarding Claims 18 and 8, Yeom in view of Schmidt doesn’t explicitly teach the claim limitation. However, Falahatpisheh superimposing velocity vectors or streamlines on the blood flow velocity field determined by wOFV to determine residence time of a blood cell along flow path in the microchannel [Para. 37-41]. It would have been obvious to one of ordinary skill in the art before the effective filing date to modify Yeom in view of Schmidt to teach the claim limitation, feature as taught by Falahatpisheh; because the modification improves how you get 3D velocity fields from volumetric ultrasound especially for blood flow and giving a platform to validate 3D PIV methods. Claims 20, 21, 10 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over (Yeom “Microfluidic system for monitoring temporal variations of hemorheological properties and platelet adhesion in LPS-injected rats”) in view of Schmidt (“improvements in the accuracy of wavelet-based optical flow velocimetry (wOFV) using an efficient and physically based implementation of velocity regularization”), further in view of KWON (Pub. No. US 2018/0321273). Regarding Claims 20, 21, 10 and 11, Yeom in view of Schmidt doesn’t explicitly teach the claim limitation. However, KWON teaches wherein the plurality of images are obtained by two cameras that provide staggered image acquisition of the blood flowing through the microchannel, wherein both cameras operate at continuous framing but are triggered such that the second camera acquires its images a time at after the images acquired by the first camera [fig. 1, 6, and corresponding description]. It would have been obvious to one of ordinary skill in the art before the effective filing date to modify Yeom in view of Schmidt to teach the claim limitation, feature as taught by KWON; because the modification improves how you get 3D velocity fields from volumetric ultrasound especially for blood flow and giving a platform to validate 3D PIV methods. Conclusion Any inquiry concerning this communication or earlier communications from the examiner should be directed to SOLOMON G BEZUAYEHU whose telephone number is (571)270-7452. The examiner can normally be reached on Monday-Friday 10 AM-7 PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, O’Neal Mistry can be reached on 313-446-4912. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-0101 (IN USA OR CANADA) or 571-272-1000. /SOLOMON G BEZUAYEHU/ Primary Examiner, Art Unit 2666
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Prosecution Timeline

May 17, 2023
Application Filed
Jun 11, 2025
Non-Final Rejection — §103
Sep 15, 2025
Response Filed
Dec 26, 2025
Non-Final Rejection — §103
Mar 30, 2026
Response Filed

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Prosecution Projections

2-3
Expected OA Rounds
75%
Grant Probability
99%
With Interview (+34.8%)
3y 4m
Median Time to Grant
Moderate
PTA Risk
Based on 614 resolved cases by this examiner